Glucose forms the most ubiquitous energy source in biology. In humans, glucose is primarily derived from the breakdown of carbohydrates in the diet or in body stores (glycogen), in addition to secondary endogenous synthesis from protein or from the glycerol moiety of triglycerides. Importantly, even under diverse conditions (such as feeding, fasting and severe exercise), the blood glucose level is maintained within a fairly narrow interval, 70-120 mg/dL, by the body's homeostatic system. For an average person, this implies that the total quantity of glucose in the blood and body fluids is approximately 5 grams—a remarkably small number given the typical carbohydrate intake per day. To maintain this natural balance, an intricate set of biomolecule interactions, modulated by glucoregulatory hormones such as insulin, needs to occur. However, in people afflicted with diabetes mellitus, the defective nature of carbohydrate metabolism (stemming from inadequate insulin production, response or both) leads to the presence of high blood glucose.
Diabetes mellitus, characterized by the defective regulation of blood glucose, is the most common disorder of the endocrine system affecting nearly 24 million people in the US alone. Given the lack of suitable therapeutic options, effective glycemic control is imperative in avoiding acute and chronic complications, such as diabetic coma, and microvascular and macrovascular complications. To this end, the development of a non-invasive blood glucose sensor is pursued using a variety of optical and spectroscopic modalities. While monitoring blood glucose remains the gold standard for continuous monitoring and evaluation of treatment options, glycated hemoglobin (HbA1c) has gained approval in the medical community in assessing the long-term history of glycemic control. HbA1c is formed by the non-enzymatic glycosylation (glycation) of hemoglobin exposed to blood glucose and therefore has a strong correlation with the average glucose concentrations in the bloodstream in the preceding three month period (life span of the erythrocytes). Due to this strong correlation, HbA1c levels have been regularly used for monitoring long-term glucose control in established diabetics and has been recently approved for screening for diabetes (HbA1c≥6.5%) and pre-diabetes (5.7%≤HbA1c≤6.4%) in the United States.
Presently, HbA1c is distinguished from non-glycated hemoglobin using assay techniques such as high-performance liquid chromatography (HPLC), isoelectric focusing and immunoassay. However, the presence of hemoglobin variants and other clinical factors such as uremia may interfere with HbA1c determinations. As an alternate method for HbA1c detection, others have recently reported the application of surface enhanced resonance Raman spectroscopy (SERRS). Though promising in approach, precise quantification of the analyte of interest (HbA1c) using SERSS is difficult due to poor spectral reproducibility and generation of spurious background signals.